Stable Feature Selection for Biomarker Discovery

Feature selection techniques have been used as the workhorse in biomarker discovery applications for a long time. Surprisingly, the stability of feature selection with respect to sampling variations has long been under-considered. It is only until recently that this issue has received more and more attention. In this article, we review existing stable feature selection methods for biomarker discovery using a generic hierarchal framework. We have two objectives: (1) providing an overview on this new yet fast growing topic for a convenient reference; (2) categorizing existing methods under an expandable framework for future research and development

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Generalized gene co-expression analysis via subspace clustering using low-rank representation

BACKGROUND: Gene Co-expression Network Analysis (GCNA) helps identify gene modules with potential biological functions and has become a popular method in bioinformatics and biomedical research. However, most current GCNA algorithms use correlation to build gene co-expression networks and identify modules with highly correlated genes. There is a need to look beyond correlation and identify gene modules using other similarity measures for finding novel biologically meaningful modules. RESULTS: We propose a new generalized gene co-expression analysis algorithm via subspace clustering that can identify biologically meaningful gene co-expression modules with genes that are not all highly correlated. We use low-rank representation to construct gene co-expression networks and local maximal quasi-clique merger to identify gene co-expression modules. We applied our method on three large microarray datasets and a single-cell RNA sequencing dataset. We demonstrate that our method can identify gene modules with different biological functions than current GCNA methods and find gene modules with prognostic values. CONCLUSIONS: The presented method takes advantage of subspace clustering to generate gene co-expression networks rather than using correlation as the similarity measure between genes. Our generalized GCNA method can provide new insights from gene expression datasets and serve as a complement to current GCNA algorithms

Clustering in Conjunction with Wrapper Approach to Select Discriminatory Genes for Microarray Dataset Classification

With the advent of microarray technology, it is possible to measure gene expression levels of thousands of genes simultaneously. This helps us diagnose and classify some particular cancers directly using DNA microarray. High-dimensionality and small sample size of microarray datasets has made the task of classification difficult. These datasets contain a large number of redundant and irrelevant genes. For efficient classification of samples there is a need of selecting a smaller set of relevant and non-redundant genes. In this paper, we have proposed a two stage algorithm for finding a set of discriminatory genes responsible for classification of high dimensional microarray datasets. In the first stage redundancy is reduced by grouping correlated genes into clusters and selecting a representative gene from each cluster. Maximal information compression index is used to measure similarity between genes. In the second stage a wrapper based forward feature selection method is used to obtain a set of discriminatory genes for a given classifier. We have investigated three different techniques for clustering and four classifiers in our experiments. The proposed algorithm is tested on six well known publicly available datasets. Comparison with the other state-of-the-art methods show that our proposed algorithm is able to achieve better classification accuracy with less number of genes

Cancer prediction using graph-based gene selection and explainable classifier

Several Artificial Intelligence-based models have been developed for cancer prediction. In spite of the promise of artificial intelligence, there are very few models which bridge the gap between traditional human-centered prediction and the potential future of machine-centered cancer prediction. In this study, an efficient and effective model is developed for gene selection and cancer prediction. Moreover, this study proposes an artificial intelligence decision system to provide physicians with a simple and human-interpretable set of rules for cancer prediction. In contrast to previous deep learning-based cancer prediction models, which are difficult to explain to physicians due to their black-box nature, the proposed prediction model is based on a transparent and explainable decision forest model. The performance of the developed approach is compared to three state-of-the-art cancer prediction including TAGA, HPSO and LL. The reported results on five cancer datasets indicate that the developed model can improve the accuracy of cancer prediction and reduce the execution time

Unsupervised Algorithms for Microarray Sample Stratification

The amount of data made available by microarrays gives researchers the opportunity to delve into the complexity of biological systems. However, the noisy and extremely high-dimensional nature of this kind of data poses significant challenges. Microarrays allow for the parallel measurement of thousands of molecular objects spanning different layers of interactions. In order to be able to discover hidden patterns, the most disparate analytical techniques have been proposed. Here, we describe the basic methodologies to approach the analysis of microarray datasets that focus on the task of (sub)group discovery.Peer reviewe

Statistical methods for the analysis of RNA sequencing data

The next generation sequencing technology, RNA-sequencing (RNA-seq), has an increasing popularity over traditional microarrays in transcriptome analyses. Statistical methods used for gene expression analyses with these two technologies are different because the array-based technology measures intensities using continuous distributions, whereas RNA-seq provides absolute quantification of gene expression using counts of reads. There is a need for reliable statistical methods to exploit the information from the rapidly evolving sequencing technologies and limited work has been done on expression analysis of time-course RNA-seq data. In this dissertation, we propose a model-based clustering method for identifying gene expression patterns in time-course RNA-seq data. Our approach employs a longitudinal negative binomial mixture model to postulate the over-dispersed time-course gene count data. We also modify existing common initialization procedures to suit our model-based clustering algorithm. The effectiveness of the proposed methods is assessed using simulated data and is illustrated by real data from time-course genomic experiments. Another common issue in gene expression analysis is the presence of missing values in the datasets. Various treatments to missing values in genomic datasets have been developed but limited work has been done on RNA-seq data. In the current work, we examine the performance of various imputation methods and their impact on the clustering of time-course RNA-seq data. We develop a cluster-based imputation method which is specifically suitable for dealing with missing values in RNA-seq datasets. Simulation studies are provided to assess the performance of the proposed imputation approach

Efficient Feature Subset Selection Algorithm for High Dimensional Data

Feature selection approach solves the dimensionality problem by removing irrelevant and redundant features. Existing Feature selection algorithms take more time to obtain feature subset for high dimensional data. This paper proposes a feature selection algorithm based on Information gain measures for high dimensional data termed as IFSA (Information gain based Feature Selection Algorithm) to produce optimal feature subset in efficient time and improve the computational performance of learning algorithms. IFSA algorithm works in two folds: First apply filter on dataset. Second produce the small feature subset by using information gain measure. Extensive experiments are carried out to compare proposed algorithm and other methods with respect to two different classifiers (Naive bayes and IBK) on microarray and text data sets. The results demonstrate that IFSA not only produces the most select feature subset in efficient time but also improves the classifier performance

The importance of data classification using machine learning methods in microarray data

The detection of genetic mutations has attracted global attention. several methods have proposed to detect diseases such as cancers and tumours. One of them is microarrays, which is a type of representation for gene expression that is helpful in diagnosis. To unleash the full potential of microarrays, machine-learning algorithms and gene selection methods can be implemented to facilitate processing on microarrays and to overcome other potential challenges. One of these challenges involves high dimensional data that are redundant, irrelevant, and noisy. To alleviate this problem, this representation should be simplified. For example, the feature selection process can be implemented by reducing the number of features adopted in clustering and classification. A subset of genes can be selected from a pool of gene expression data recorded on DNA micro-arrays. This paper reviews existing classification techniques and gene selection methods. The effectiveness of emerging techniques, such as the swarm intelligence technique in feature selection and classification in microarrays, are reported as well. These emerging techniques can be used in detecting cancer. The swarm intelligence technique can be combined with other statistical methods for attaining better results